This project will establish and operate a Biotechnology Resource for Electron Probe Microanalysis. This resource will provide research groups in the Harvard Medical community with access to new and complex microanalytical instrumentation and methodologies and train them in their use. The primary instrument, an electron probe microanalyzer, is capable of localizing any chemical element heavier than boron on a submicron scale, hence within single cells in quantities less than 10 to the minus 15th power grams. It can perform complete elemental analysis on liquid samples of 10 to the minus 10th power liters. Application of this instrument to medical research has been limited because biological sample preparation methods and operating parameters have not been developed which allow the full capabilities of the instrument to be utilized. Accordingly the resource staff will conduct research in the context of collaborative projects with members of the medical community. This research will be directed toward standardizing preparation of both liquid and tissue samples, development of quantitative techniques for histochemistry, creating a "cold-tracer" methodology, and improving the instrument's utility for medical research through mechanical and electrical modifications developed in collaboration with laboratories at the Massachusetts Institute of Technology.